Germicidal compositions



United States Patent Offiee 3,152,039. Patented Oct. 6, 1964 3,152,039GERMICIDAL COMPOSITIONS Guy C. Mattson, Midland, Mich, assignor to TheDow Chemical Company, Midland, Mich., a corporation of Delaware NoDrawing. Filed Nov. 23, 1960, Ser. No. 71,171 13 Claims. (Cl. 167-31)The invention relates to germicidal compositions and more particularlyis concerned with germicidal compositions comprising brominatedsalicylanilides dissolved in an alcoholic solvent to which has beenadded an alkanolamine.

Brominated salicylanilides such as 3,5,4'-tribrornosalicylanilide,3,5-dibromosalicylanilide, 4',5-dibromosalicylanilide and mixtures ofsuch triand dibrominated compounds exhibit excellent germicidalproperties. However, the utility of these substances is limited to someextent by their low solubility in most common solvents, e.g. ethylalcohol, propylene glycol, glycerine, isopropanol, acetone, and thelike.

This low solubility not only limits the use of these substances incompositions wherein it is desirable to have the germicide in adissolved state, i.e., shampoos, deodorants, etc., but also makesdiificult the incorporation of these germicides into compositions wherethey are used in the insoluble state such as in soap and detergent bars,powders and flakes.

Now unexpectedly it has been found that the solubility of3,5,4-tribromosalicylanilide, di-dibromosalicylanilides and mixtures ofthe triand di-brominated materials in common alcoholic type solvents canbe greatly increased by adding a small amount of an alkanolaminethereto.

The compositions of the instant invention comprise3,5,4-tribromosalicylanilide and a dibromosalicylanilide in a solventmixture of a monohydroxy aliphatic hydrocarbon alcohol, polyhydroxyaliphatic hydrocarbon alcohol or a polyglycol and a mono-, di ortrialkanolamine wherein the amount of the alkanolamine in thecomposition ranges up to about 40 weight percent of the solvent mixture.

Preferably, in the instant composition the triand dibromosalicylanilideswill be used as a mixture containing from about 25 to about 98 weightpercent of the tribrominated compound and from about 75 to about 2weight percent of the dibromosalicylanilide and desirably will be usedas a mixture containing about 80 parts by weight of thetribromosalicylanilide and about 20 parts by Weight of thedibromosalicylanilide. The actual concentration of the members used inthe instant germicidal composition ordinarily will be limited to thoseamounts below which saturated solutions are formed with the solvents.The monoand polyhydroxy alcohols, polyglycols and alkanolaminespreferably all will have alkyl groups selected from those memberscontaining 2 and 3 carbon atoms and the amount of alkanolamine to beused desirably will range from about 5 to about 20 weight per cent ofthe weight of the solvent mixture.

Of the common solvents and carriers for brominated salicylanilides,hydrocarbon aliphatic alcohols such as absolute ethanol, ethyleneglycol, 95 percent ethanol, polyethylene glycols, propanol, isopropanol,glycerine, polypropylene glycols, propylene glycol and the like areparticularly adapted for incorporation into conventional soap anddetergent compositions. By the term soap is meant sodium salts ofvarious fatty acids of natural oils and fats and mixtures of such sodiumsalts. This term is also meant to include compounds of these fatty acidswherein other metal or basic radicals are present instead of sodium. Bythe term detergent is meant a material which has a cleansing action likesoap but is not derived directly from fatty acids. (See Rose and Rose,The Condensed Chemical Dictionary, 5th edition, Reinhold PublishingCorporation, New York.) However, the brominated salicylanilides enjoyonly a limited solubility in most of these solvent materials. Forexample, the solubility of a mixture of 3,5,4'-tribromosalicylanilide(about weight percent) and 3,S-dibromosalicylanilide (about 20 weightpercent) based on grams of the salicylanilide mixture per 100 grams ofsolvent at 25 C. is; 0.35 gram in propylene glycol, 0.012 gram inglycerine, 0.92 gram in isopropanol, 0.03 gram in percent ethanol, and0.03 gram in absolute ethanol. The solubility in the polyglycols issomewhat improved, e.g. 5.38 grams per grams of a polypropylene glycolhaving an average molecular weight of about 4000 and 20.9 grams per 100grams of a polyethylene glycol of average molecular weight about 400.However, with all of these solvents, replacement of only a small amountof the alcoholic member by an alkanolamine has been found tounexpectedly increase the solubility of the brominated salicylanilidetherein. To illustrate, 100 grams of a solution of 95 percent ethanol(90 weight percent) and diethanolamine (10 weight per cent) was found todissolve 37 grams of the 80 weight per cent 3,5,4,-tribromo- 20 weightpercent 3,S-dibromosalicylanilide mixture.

Compositions containing larger amounts of the alkanolamines show stillincreased solubility of the brominated salicylanilides. However, formost applications, and, particularly when the germicide compositions areused in toilet and laundry soaps, it is desirable to keep thealkanolamine content relatively low, e.g. below about 20 percent of thetotal composition.

The compositions will be used in soaps at an eifective germicidalconcentration, e.g. in amounts ranging from about 0.05 to about 1.0weight percent, based on the total brominated salicylanilideconcentration present in the salicylanilidealcohol orpolyglycolalkanolamine solution.

The actual preparation of the instant germicidal compositions can becarried out by various conventional techniques. For example, thealkanolamine can first be added to the alcoholic solvent member and thebrominated salicylanilide can then be added to the mixed solvent anddissolved therein. Alternatively, a given amount of a brominatedsalicylanilide or salicylanilide mixture can be added to an alcohol andsuflicient alkanolamine then be added to this mixture to produce thedesired solution.

The instant compositions have been found in a standard microorganismgrowth control test to give growth inhibition to a number of commonmicroorganisms at about the same level as the brominated compoundsthemselves. Such action demonstrates that the germicidal activity of thebrominated salicylanilides is not lost by their incorporation into thesecompositions.

Toxicological studies have indicated that there appears to be nocontraindications for the use of these solutions in formulationsdesigned for direct human contact, e.g.

3 shampoos, deodorants, toilet soaps and detergents and the like.

The following examples will serve to further illustrate the compositionsof the instant invention but are not meant to limit it thereto.

Example 1 A weighted sample of a mixture containing about 80 parts3,5,4'-tribromosalicylanilide and about 20 parts 3,5-dibromosalicylanilide was placed in a beaker. Ninetyfive percentethanol-alkanolamine solvent was added with stirring at room temperature(about 25 C.) until complete dissolution of the sample occurred, asdetermined by visual observation.

The results of test runs using 90/10 (by volume) mixtures of 95 percentethanol-diethanolamine and 95 percent ethanol-triethanolamine arepresented as follows:

A weighted sample of the brominated salicylanilide mixture described inExample 1 was added at about room temperature, 25 C., to a given amountof an alcoholic solvent contained in a flask. The amount of thesalicylanilide mixture used in all cases was markedly in excess of thatwhich was soluble in the given amount of the alcohol. Controlled amountsof an alkanolamine were added with stirring to the mixture. Thisaddition was stopped at the point where complete solubility of thesalicylanilides in the resulting alcohol-alkanolamine solvent mixturewas observed. The following table lists the resulting compositionsobtained from several test runs.

lowing table lists the resulting germicidal solution compositions:

Brominated Sali- Alcohol Alkanolamine ylanilides Composition N 0. PartsBy Weight 1 3,5,4'-Tribromo- Propylene GlycoLMonoethanolasalicylanilide] mine. 3,5-dibromosalicylanilide GlycerineDo. Ethanol (95%). Do. Propylene Glycol- Monolsopropanolamine. GlyceriueDo. Ethanol (95%)--.- Do.

Propylene Glycol- Dusopropanolamine. Glycerine Do.

A second series of tests was run utilizing the same components as above,but in this series the solvent pair contained 30 parts by weight of theamine and 50 parts by weight of the alcoholic material. This isequivalent to a solvent containing about 37.5 weight percent of aminecomponent. To these solvent pairs was added parts by weight of thebrominated salicylanilide mixture.

The resulting compositions all were found to form solutions except forthe system employing the monoisopro panolamine and glycerine solventpair.

Example 4 The germicidal activity of several compositions of the instantinvention was studied utilizing a standard bacteriostatic test. In thistest, a predetermined quantity of the germicidal composition containingan 80-20 mixture of 3,5,5'-tribromo and 3,5-dibromosalicylanilide, andbased on actual brominated salicylanilide concentration, wasincorporated into a melted Difco nutrient agar medium. The agar was thenhardened. One of a variety of microorganisms was streaked onto thehardened medium and the culture then was incubated at 30 C. for 72hours.

Alcoholic Component Alkanolamine Component Solubility Bromin- Salicyl-Rlm No. ated Salianilide/ cylanilide, solvent,

grams Type Grams Type Grams g.ll00 g 1 Polyethylene GlycolTriethanolamine 5 54. 5 2 50 50 10 82. 3 3 10 Glycerine 186 4. 5 5. 25

1 Average molecular weight=400.

Example 3 A number of stock solvent solutions were prepared containing15 parts by weight of a given alkanolamine and 75 parts by weight of agiven alcoholic member. To each of these solutions, suflicientquantities of the brominated salicylanilide mixture described in Example1 were added to give a resulting composition containing about 10 percentby weight of the brominated salicylanilide. In all cases, completesolubility of the salicylanilide mixture was found in the solvent pair.The folefliciency.

Germieidal Composition I (p.p.m. llI (p.p.m. Control 3 Run No.Microorganism (p.p.m.)

Inh No Inh 4 No 11111 4 No Inh 5 11111 5 Inh 5 Micrococcus pyogenes 5 55 (staph. aureus).

Salmonella typhosa 50 01% 50 50 Aerobacter aerogenes .01% 50 .01% .01%Erwim'a carolovora 50 10 50 10 50 (4 80-20 3,5,4'-tribromo-,3,5-dibromosalicylanilide (40 parts by Wt.), Propylene Glycol 5 parts byat), Diethanolamine parts by wt parts by 1.), Monoethanolamine (40 partsby wt.).

3 80 parts 3,5,4-tribromosalicylanilide, parts 3,fidibromosalicylanilide.

4 Lowest concentration of germicide to give growth inhibition. 5 Highestconcentration of germicide that gave no growth inhibition. 6 Unlessshown otherwise.

In a manner similar to that described for the foregoing examples, amixture of about 98 parts by Weight of 3,5,4'-tribrominatedsalicylanilide and about 2 parts by weight of 4',5-dibromosalicylanilideand a mixture containing about weight percent of3,5,4-tribromosalicylanilide and about 75 weight percent of 3,5-dibromosalicylanilide can be dissolved in alcoholic-alkanolamine solvents asdefined herein to yield effective germicidal compositions.

Various modifications can be made in the compositions of the presentinvention without departing from the spirit or scope thereof for it isunderstood that I limit myself only as defined in the appended claims.

I claim:

1. A germicidal composition comprising a solution of a mixture of3,5,4-tribromosalicylanilide and a dibromosalicylanilide in a mixedalcoholic-alkanolamine solvent, said mixed solvent dissolving markedlyincreased amounts of the brominated salicylanilide mixture over thatdissolvable by the alcoholic component alone, the alcoholic component ofsaid solvent being a member selected from the group consisting ofmonohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatichydrocarbon alcohols and polyglycols having an alkyl group containingfrom 2 to 3 carbon atoms, the alkanolamine being a member selected fromthe group consisting of mino-, diand trialkanolamines wherein the alkylgroup contains from 2 to 3 carbon atoms and the amount of saidalkanolamine in the solvent mixture being up to percent of the weight ofsaid solvent mixture.

2. A germicidal composition comprising a solution of a mixture of3,5,4'-tribromosalicylanilide and a dibromosalicylanilide in a solventmixture of an alcohol and an alkanolamine, said mixture of brominatedsalicylanilides containing from about 25 to about 98 percent of thetribrominated compound and from about 75 to about 2 weight percent ofthe dibromosalicylanilide and said mixture being present in aconcentration below which said solution is saturated with said mixture,said solvent mixture dissolving an amount of the brominatedsalicylanilides greater than that dissolved by the alcoholic componentalone and said solvent mixture comprising a mixture of (1) a memberselected from the group consisting of monohydroxy aliphatic hydrocarbonalcohols, polyhydroxy aliphatic hydrocarbon alcohols and polyglycolshaving an alkyl group containing from 2 to 3 carbon atoms and (2) amember selected from the group consisting of mono-, di andtrialkanolamine having an alkyl group containing from 2 to 3 carbonatoms, the alkanolamine comprising up to about 40 weight percent of theweight of the solvent mixture.

3. A germicidal composition comprising a solution of a mixturecontaining about 80 parts by weight of 3,5,4- tribromosalicylanilide andabout 20 parts by weight of a dibromosalicylanilide dissolved in a mixedalcoholicalkanolamine solvent, the brominated salicylanilide mixturebeing present in said solution at a concentration below which saidsolution is saturated with said mixture, said mixedalcoholic-alkanolamine solvent comprising (1) a member selected from thegroup consisting of monohydroxy aliphatic hydrocarbon alcohols,polyhydroxy aliphatic hydrocarbon alcohols and polyglycols and (2) amember selected from the group consisting of monodiand trialkylamineswherein the alcoholic member and amine each have alkyl groups containingfrom 2 to 3 carbon atoms, said alkanolamine comprising from about 5 toabout 20 percent of the weight of said solvent mixture, and said solventmixture dissolving markedly increased amounts of said brominatedsalicylanilide mixture over that dissolved by the alcoholic componentalone.

4. A soap composition which comprises soap having an efiectivegermicidal concentration of a mixture of 3,5,4-tribromosalicylanilideand a dibromosalicylanilide in a solvent, said mixture ofsalicylanilides containing from about 25 to about 98 percent of thetribrominated compound and from about to about 2 weight percent of thedibromosalicylanilide and said mixture being present in a concentrationbelow which said solution i saturated with said mixture, said solventcomprising a mixture of (1) a member selected from the group consistingof monohydroxy aliphatic hydrocarbon alcohols, polyhydroxy aliphatichydrocarbon alcohols and polyglycols having an alkyl group containingfrom 2 to 3 carbon atoms and (2) a member selected from the groupconsisting of mono-, diand trialkanolamines having an alkyl groupcontaining from 2 to 3 carbon atoms, the alkanolamine comprising up toabout 20 weight percent of the weight of the solvent mixture.

5. A germicidal solution which comprises:

(a) up to about 10 parts by weight of a mixture containing aboutpercent, 3,5,4'-tribromosalicylanilide and about 20 percent3,S-dibromosalicylanilide,

(b) about 75 parts by weight of an alcoholic member selected from thegroup consisting of monohydroxy aliphatic hydrocarbon alcohols,polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having analkyl group containing from 2 to 3 carbon atoms, and

(0) about 15 parts by weight of an alkanolamine selected from the groupconsisting of mono-, diand trialkanolamines wherein the alkyl groupcontains from 2 to 3 carbon atoms.

6. A germicidal solution which comprises:

(a) up to about 20 parts by weight of a mixture containing about 80percent 3,5,4-tribromosalicylanilide and about 20 percent3,S-dibromosalicylanilide,

(b) about 30 parts by weight of an alkanolamine selected from the groupconsisting of mono-, diand trialkanolamines wherein the alkyl groupcontains from 2 to 3 carbon atoms, and

(0) about 50 parts by weight of an alcoholic member selected from thegroup consisting of monohydroxy aliphatic hydrocarbon alcohols,polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having analkyl group containing from 2 to 3 carbon atoms.

7. A germicidal solution consisting essentially of:

(a) a mixture of about 80 parts by weight 3,5,4'-tribromosalicylanilideand about parts by weight 3,5-dibromosalicylanilide, and

(b) a solvent of 95 ethanol-diethanolamine, said solvent comprising on avolume basis about 90 parts of said 95% ethanol and about 10 partsdiethanolamine, said solvent of said ethanol-diethanolamine dissolvingat about C. up to about 37 grams of said brominated salicylanilidemixture per 100 milliliters of said ethanol-diethanolamine solvent.

8. A germicidal solution comprising:

(a) up to about parts by Weight of a mixture containing about 80 percent3,5,4'-tribromosalicylanilide and about 20 percent3,5-dibromosalicylanilide,

(b) about 50 parts by Weight polyethylene glycol, and

(c) from about 5 to about 10 parts by weight triethanolamine.

9. A germicidal solution comprising:

(a) up to about 10 parts by weight of a mixture containing about 80percent 3,5,4'-tribromosalicylanilide and about 20 percent3,S-dibromosalicylanilide,

(b) about 186 parts by weight glycerine, and

(c) about 4.5 parts by weight triethanolamine.

10. A germicidal solution which comprises:

(a) up to about 40 parts by weight of a mixture containing about 80percent 3,5,4'-tribrornosalicylanilide and about 20 percent3,5-dibromosalicylanilide,

(b) about parts by weight propylene glycol, and

(0) about 15 parts by weight diethanolamine.

11. A germicidal solution which comprises:

(a) up to about 40 parts by weight of a mixture containing about 80percent 3,5,4'-tribromosalicylanilide and about 20 percent3,S-dibromosalicylanilide,

(b) about 20 parts by weight 95% ethanol, and

(c) about 40 parts by weight monoethanolamine.

12. A detergent composition which comprises detergent having aneffective germicidal composition of a mixture 8 of3,5,4'-tribromosalicylanilide and a dibrornosalicylanilide in a solvent,said mixture of salicylanilides containing from about 25 to about 98percent of the tribrominated compound and from about to about 2 weightpercent of the dibromosalicylanilide and said mixture being present in aconcentration below which said solution is satu rated with said mixture,said solvent comprising a mixture of (1) a member selected fromthe'group consisting of monohydroxy aliphatic hydrocarbon alcohols,polyhydroxy aliphatic hydrocarbon alcohols and polyglycols having analkyl group containing from 2 to 3 carbon atoms and (2) a memberselected from the group consisting of mono-, diand trialkanolamineshaving an alkyl group containing from 2 to 3 carbon atoms, thealkanolamine comprising up to about 20 weight percent of the Weight ofthe solvent mixture.

13. A germicidal solution consisting essentially of:

- (a) a mixture of about parts by Weight 3,5,4'-tribromosalicylanilideand about 20 parts by weight 3,5-dibromosa1icylanilide, and

(b) a solvent of 95% ethanol-triethanolamine, said solvent comprising ona volume basis about parts of said ethanol and about 10 parts oftriethanolamine, said ethanol-triethanolamine solvent dissolving atabout 25 C. up to about 20 grams of said brominated salicylanilidemixture per milliliters of said ethanol-triethanolamine solvent.

References Cited in the file of this patent UNITED STATES PATENTS2,485,339 Eijk Oct. 18, 1949 2,643,965 OBrien June 30, 1953 2,731,386Reiner Jan. 17, 1956 2,865,861 Stephens Dec. 23, 1958 2,906,711 SteckerSept. 29, 1959 2,948,684 Thiele Aug. 9, 1960 OTHER REFERENCES Sagarin:Cosmetics Science and Technology, published by Interscience Publishers,Inc., New York (1957),

pages 292, 293 and 296.

1. A GERMICIDAL COMPOSITION COMPRISING A SOLUTION OF A MIXTURE OF3,5,4''-TRIBROMOSALICYLANILIDE AND A DIBROMOSALICYLANILIDE IN A MIXEDALCOHOLIC-ALKANOLAMINE SOLVENT, SAID MIXED SOLVENT DISSOLVING MARKEDLYINCREASED AMOUNTS OF THE BROMINATED SALICYLANILIDE MIXTURE OVER THATDISSOLVABLE BY THE ALCOHOLIC COMPONENT ALONE, THE ALCOHOLIC COMPONENT OFSAID SOLVENT BEING A MEMBER SELECTED FROM THE GROUP CONSISTING OFMONOHYDROXY ALIPHATIC HYDROCARBON ALCOHOLS, POLYHYDROXY ALIPHATICHYDROCARBON ALCOHOLS AND POLYGLYCOLS HAVING AN ALKYL GROUP CONTAININGFROM 2 TO 3 CARBON ATOMS, THE ALKANOLAMINE BEING A MEMBER SELECTED FROMTHE GROUP CONSISTING OF MINO-, DI- AND TRIALKANOLAMINES WHEREIN THEALKYL GROUP CONTAINS FROM 2 TO 3 CARBON ATOMS AND THE AMOUNT OF SAIDALKANOLAMINE IN THE SOLVENT MIXTURE BEING UP TO 40 PERCENT OF THE WEIGHTOF SAID SOLVENT MIXTURE.